A Study of the Effectiveness and Safety of Risperidone to Augment SSRI Therapy in Patients With Treatment-Resistant Depression
Information source: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information obtained from ClinicalTrials.gov on December 31, 2007
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Depression; Depressive Disorder, Major; Depressive Disorder
Intervention: risperidone (Drug)
Phase: Phase 3
Sponsored by: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Official(s) and/or principal investigator(s):
Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Clinical Trial, Study Director, Affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
The purpose of this study is to evaluate the effectiveness and safety of risperidone to
augment SSRI therapy in patients with treatment-resistant depression and to demonstrate the
long-term maintenance effect of risperidone as augmentation therapy compared with placebo
augmentation in these patients.
Official title: A Study to Evaluate the Efficacy, Safety and Maintenance Effect of Risperidone Augmentation of SSRI Monotherapy in Young and Older Adult Patients With Unipolar Treatment-Resistant Depression
Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at end of treatment; time to relapse
Secondary outcome: Response rate, determined from >=50% improvement from baseline at MADRS total score; change from baseline in Hamilton Rating Scale of Depression (HAM-D) and Clinical Global Impression (CGI) scale; incidence of adverse events throughout study.
Treatment strategies for treatment-resistant depression (TRD) involve either switching to
another antidepressant, augmenting the first-line treatment with various pharmacologic
agents, or switching to a different medication in combination with another agent. This study
includes 2 phases: an open-label treatment phase and a double-blind maintenance phase, during
which neither the patient nor the physician knows whether risperidone or placebo is
administered. The open-label phase has an initial period of 6 weeks during which patients
with TRD receive only citalopram, a selective serotonin reuptake inhibitor (SSRI).
Risperidone is then added to the treatment regimen for 4 weeks to evaluate its short-term
effect in augmenting the therapy. The double-blind phase last for 6 months and evaluates the
relapse prevention of continued risperidone augmentation therapy compared with placebo
augmentation of the SSRI. Targeted daily doses of citalopram and risperidone are adjusted for
younger adults (18 to 54 years of age) and older adults (55 to 85 years of age). Assessments
of effectiveness include the Montgomery-Asberg Depression Rating Scale (MADRS); Hamilton
Rating Scale of Depression (HAM-D); Clinical Global Impression of Severity (CGI-S); response
rate, determined by the proportion of patients showing >=50% improvement on MADRS total
score; and relapse, evaluated by changes in CGI or HAM-D scores. Safety evaluations include
the incidence of adverse events throughout the study, vital signs (pulse and blood pressure)
and weight, and clinical laboratory tests (hematology, biochemistry, urinalysis) at specified
intervals. The study hypothesis is that risperidone augmentation of SSRI therapy will show
significant improvement in symptoms of depression compared with SSRI monotherapy and that
risperidone augmentation will show better time-to-relapse than placebo augmentation in
patients with TRD.
Once daily, oral tablets of risperidone (0. 25 milligram[mg], 0. 5mg, 1. 0mg, and 2. 0mg),
citalopram (20mg and 40mg) or placebo. Risperidone for 30 weeks; 0. 25-2. 0mg for younger
adults, 0. 25-1. 0mg for older adults. Citalopram for 36 weeks; 20-60 mg for younger adults;
20-40 mg for older adults.
Minimum age: 18 Years.
Maximum age: 85 Years.
Meet criteria of Diagnostic and Statistical Manual of Mental Diseases, 4th edition
(DSM-IV), for Major Depressive Disorder
History of resistance to therapy with antidepressant medication
Score on the Hamilton Rating Scale of Depression (HAM-D) of >=20 at start of
Meet DSM-IV criteria for Axis I disorder (except anxiety disorders) or borderline
Substance dependence, including drugs of abuse and alcohol
History of schizophrenia, bipolar disorder, or manic episode
Meet DSM-IV criteria for delirium, dementia, amnesic or other cognitive disorder supported
by Mini Mental Status Examination (MMSE)
Pregnant or nursing females, or those lacking adequate contraception
Locations and Contacts
A Study to Evaluate the Efficacy, Safety and Maintenance Effect of Risperidone Augmentation of SSRI Monotherapy in Young and Older Adult Patients with Unipolar Treatment-Resistant Depression
Ending date: March 2004
Last updated: May 18, 2007